Abstract A water-soluble, inexpensive, and biocompatible polymer with unique properties and processing characteristics has been proven effective against multiple serine and metalloproteases in testing. The polymer is used to formulate wound therapies that offer an alternative to existing costly products. The major specific aim(s) of this work detail the formulation and animal evaluation of a hydrogel dressing that releases the water-soluble polymer agent in order to control the proteolytic environment of a chronic wound as well as deliver a secondary agent such as an anti-oxidant. This simple and rational therapy is based upon the idea that controlling proteolysis in a chronic wound environment could result in a more favorable healing environment. The polymer technology described herein may have application beyond wound therapies where controlling proteases and delivering a secondary agent simultaneously may be beneficial. Conservative estimates suggest that over 2 million people annually in the U.S. suffer from chronic ulcers (Rees et. al., 1999) and these numbers are expected to increase in view of the aging population and the rise of diabetes. The prevalence of diabetes for all age-groups worldwide has been estimated to be 2.8% in 2000 and will rise to 4.4% in 2030. Accordingly, the total number of people with diabetes is projected to approach 366 million in 2030. Among persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. In addition, the incidence of ulcer recurrence after complete healing approaches 30% within 12 months. Diabetic foot ulcers cause substantial emotional, physical, productivity, and financial losses. The estimated cost of treating a diabetic foot ulcer in 1999 was $18,000. In instances requiring amputation, these costs jumped to $28 000. These estimates do not take into account the personal and socioeconomic impact of these wounds on a patient's life. A wound treatment that utilizes a commercially available & inexpensive, water- soluble polymer of tailorable utility that leverages our fundamental understanding of the underlying biology and biochemistry of chronic wounds in order to provide a multifaceted treatment is the subject of our investigation. The water-soluble polymer will be formulated into a dressing of three derivative forms that will be evaluated for their capacities to control the levels of certain damaging wound proteases via inhibition, and affect the wound by additionally delivering an NO donor, an NO precursor, or an antioxidant to the wound site. [unreadable] [unreadable] [unreadable] [unreadable]